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Molecular Biomedicine

Decoding neuro-tumor interactions in pancreatic cancer: mechanisms, immunosuppressive networks and therapeutic opportunities

This review systematically examines the molecular mechanisms of perineural invasion (PNI) in pancreatic ductal adenocarcinoma, proposes a unified four-stage model spanning mutual chemotaxis between tumors and nerves, adhesion and invasion at the tumor-nerve interface, extracellular matrix remodeling, and neural plasticity alterations, defines the perineural invasion microenvironment as a neuro-immune privileged sanctuary, and summarizes therapeutic strategies targeting the neuro-immune-tumor axis, ongoing clinical trials, and the applications of multi-omics and artificial intelligence in PNI diagnosis, mechanistic discovery, and therapeutic optimization.